E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses

Summary Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63‐linked polyubiquitination of Pelle, an interleukin‐1 (IL‐1) receptor‐associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non‐redundant roles of mam...

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Bibliographic Details
Published in:Immunological reviews 2015-07, Vol.266 (1), p.109-122
Main Authors: Medvedev, Andrei E., Murphy, Michael, Zhou, Hao, Li, Xiaoxia
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - immunology
Humans
Immunotherapy
inflammation
innate immunity
Molecular Targeted Therapy
Nuclear Proteins - metabolism
Organ Specificity
pattern recognition receptors
Receptors, Pattern Recognition - metabolism
Signal Transduction
T-Lymphocytes - immunology
ubiquitin
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
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Summary:Summary Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63‐linked polyubiquitination of Pelle, an interleukin‐1 (IL‐1) receptor‐associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non‐redundant roles of mammalian Pellino‐1, Pellino‐2, and Pelino‐3 in signaling pathways emanating from IL‐1 receptors, Toll‐like receptors, NOD‐like receptors, T‐ and B‐cell receptors. While Pellinos ability to interact with many signaling intermediates suggested their scaffolding roles, recent findings in mice expressing ligase‐inactive Pellinos demonstrated the importance of Pellino ubiquitin ligase activity. Cell‐specific functions of Pellinos have emerged, e.g. Pellino‐1 being a negative regulator in T lymphocytes and a positive regulator in myeloid cells, and details of molecular regulation of receptor signaling by various members of the Pellino family have been revealed. In this review, we summarize current information about Pellino‐mediated regulation of signaling by pattern recognition receptors, T‐cell and B‐cell receptors and tumor necrosis factor receptors, and discuss Pellinos roles in sepsis and infectious diseases, as well as in autoimmune, inflammatory, and allergic disorders. We also provide our perspective on the potential of targeting Pellinos with peptide‐ or small molecule‐based drug compounds as a new therapeutic approach for septic shock and autoimmune pathologies.
ISSN:0105-2896
1600-065X
DOI:10.1111/imr.12298